Carbon diastereoselective synthesis

Another example of a [2s+2sh-1c+1co] cycloaddition reaction was observed by Barluenga et al. in the sequential coupling reaction of a Fischer carbene complex, a ketone enolate and allylmagnesium bromide [120]. This reaction produces cyclopentanol derivatives in a [2S+2SH-1C] cycloaddition process when -substituted lithium enolates are used (see Sect. 3.1). However, the analogous reaction with /J-unsubstituted lithium enolates leads to the diastereoselective synthesis of 1,3,3,5-tetrasubstituted cyclohexane- 1,4-diols. The ring skeleton of these compounds combines the carbene ligand, the enolate framework, two carbons of the allyl unit and a carbonyl ligand. Overall, the process can be considered as a for-... 

In the enantioselective synthesis, the asymmetry (i.e., the stereoselectivity) is induced by the external chiral catalyst, while the diastereoselective synthesis does not require a chiral catalyst. The stereogenic center already present in the molecule is able to induce stereoselectivity, assuming that the synthesis starts with a single enantiomer. For instance, imagine that an a,/ -substituted product is formed, and that the reactant already contains a stereogenic carbon at a. If the reaction of (aS) leads, e.g., largely to (aS, / R) and hardly to the (aS, /IS) diastereomer (i.e., stereoisomers that are not mirror-images of each other), the reaction is diastereoselective (Scheme 14.2). 

An important example of heterogeneous diastereoselective synthesis by catalytic way is the synthesis of prostaglandines (a family of compounds having the 20-carbon skeleton of the prostanoic acid) (Scheme 14.14). Naturally, these molecules are biosynthesized via a cyclooxygenase enzyme system that is widely distributed in mammalian tissues. Many of the synthetic routes [272] involve the diastereoselective hydrogenation of a carbonylic bond having a C=C double bond... 

An expeditious and highly diastereoselective synthesis of (Z)-2-alkylsulfenyl (or 2-cyano) -2,4-diarylthietanes 53 has been reported by nucleophile (CN, RS") induced cyclization of the corresponding O,O-diethyl 5-(l,3-diaryl-3-oxopropyl) phosphorodithionates under microwave irradiation in solvent free conditions <02S1502>. This reductive cyclization can be considered to be induced by the attack of a hydride ion on the carbonyl carbon of the Michael adduct precursor to give an alkoxide ion, which attacks the phosphorus atom intramolecularly. 

For complexes of type 10 (with a hydrogen at the carbene carbon) a synthesis was worked out in which a formamide is first reacted with K2[Cr(CO)j] followed by reaction with TMSCI [7]. This way, the non-racemic formamide 12 leads to the chirally modified amino carbene complex 13, which serves as starting material for the diastereoselective synthesis of various optically active yff-lactams [8]. An example is the (formal) total synthesis of 1-carbacephalothin 16, a carbon analog of the cephalosporins (Scheme 5) [8b]. In this case, the complex 13 is irradiated in the presence of in situ prepared imine 14 to afford the /(-lactam with high dia-stereoselectivity but only in modest yield. The product (15) could (in principle) be converted in to the target compound 16. 

Although many tools have been developed for use in the prediction of the outcomes of ionic reactions, some are also applicable to the prediction of the outcomes of free radical reactions. One of the most widely used ionic reactions in diastereoselective synthesis is addition of a nucleophile (Nu-) to the carbonyl group of chiral compound RM20 CLMS, where L, M and S represent, respectively, the largest, the middle-sized and the smallest of the substituents (other than the keto group) on the asymmetric carbon (Scheme 7.17). 

In many cases various proton sources, solvents, auxiliaries, and conditions have been applied in order to obtain different diastereoselectivites from the protonation of nonstereogenic car-banion centers. However, only the tw o extreme diastereomeric product ratios are given in this section. In most experiments kinetically controlled protonation can be assumed. However, since the anionic substrate already carries one (or more) stereogenic center, selective equilibration at the newly formed stereogenic carbon - hydrogen center could increase the diastereoselec-tivity. Indeed, epimerization of this center is a valuable tool for diastereoselective synthesis, provided that the carbon-hydrogen bond is acidic enough (see enolates, Section 2.1.3.1). 

The diastereoselective synthesis of a 7 -chirogenic p-aminophosphine ligand 300 by carbon-carbon bond formation of the ethano bridge in a 3 1 ratio via reaction of an a-metallated f -chiral phosphine borane (5)-297 with a benzaldimine was described. The major diastereoisomeric p-aminophosphine borane (Sp)-298 was separated and decomplexed into the corresponding p-aminophosphine (5p)-300 under neutral conditions and without epimerization by heating at reflux in EtOH (Scheme 100) [198]. 

A reported diastereoselective synthesis of precursor A of vitamin D3 involved the use of 2-methylcyclopent-2-enone as starting material. The Mukaiyama-Michael conjugate addition of ketene acetal 269 in the presence of trityl hexachloroaniimonate afforded the adduct 270. The lateral chain was introduced, according the procedure of Tsuji, by the treatment of crude 270 with allyl carbonate and palladium dibenzylideneacetone " (Scheme 63). The expected product 271 was obtained in 63% yield from 269. Reduction of 271 with LAH afforded a mixture of diols that was selectively tosylated at the primary hydroxy group. The secondary hydroxy group was protected with the methoxymethyl group and further functional modifications afforded the lactone 272. The reaction of lithium dimethyl methylphosphonate with the lactone 272 completed the synthesis of the AB-des-cholestane derivative 273. 

Gold-catalysed cycloisomerization of l,7-diyn-3,6-bis(propargyl carbonate)s provide for a diastereoselective synthesis of naphtho[ ]cyclobutenes by a cascade sequence involving gold-catalysed double [3,3]-rearrangement, 6 r-electrocyclic reaction, and a decarbonylative cyclization (Scheme 15). °... 

Azetidines are compounds of interest in the field of agricultural and pharmaceutical chemistry. They are also useful as monomers and cross-linkers in polymer industry. Due to ring strain associated with it, azetidines are also useful S5mthons in organic chemistry. The common methods for S5mthesis of azetidines are cyclizations of y-amino alcohols, y-amino halides, 3-amino allenes, reactions of 1,3-dielectrophiles with amines, metal-catalyzed cyclizations in diazocarbonyls, cycloaddition reactions, and reduction of 2-azetidinones. There are several reports in literature on the S5mthesis of azetidines in aqueous media. A diastereoselective synthesis of azetidines is reported by the reaction of azazirconacyclopentane derivatives with iodine followed by treatment with aqueous potassium carbonate [26]. 

Rather than relying upon self-assembly processes, it is also possible to synthesize metaldirect formation of metal-carbon bonds. Tilley and Schafer have reported a unique, diastereoselective synthesis of zirconocene-containing metallamacrocycles [82]. As outlined in Scheme 6.30, treatment of racemic BINOL-based diyne 234 with Negishi-type zirconocene coupling conditions led to the diastereoselective formation of only two enantiomeric stereoisomers of metallamacrocycle (R,R)- and (S,S)-235 in an excellent 91% yield. Use of (R)-234 gave the expected homochiral enantiopure macrocycle (R,R)-235, confirming the diastereoselectivity of this process. 

So far only one example for the successful use of acetals in diastereoselective a-functionalization of chiral isotopically labeled imides has been published. Though this reaction was performed with carbon-13 material, there is little doubt that it is also applicable in carbon-14 synthesis. The titanium enolate prepared from (45)-4-benzyl-3-[(2R)-2-[ C, H3]methylpropionyl]-l,3-oxazolidin-2-one (111) reacted with trioxane to afford the corresponding a-hydroxymethyl derivative 112 in 83% yield and >96%... 

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